This is an open-label, single centre, Phase I study to determine the brain exposure of [11C]osimertinib in patients with EGFRm NSCLC with brain metastases.
Name: Osimertinib
Description: Osimertinib 80 mg once daily p.o. will be taken continuously by the patient from the day of the second PET exam.Type: Drug[11C]osimertinib + oral osimertinib
Name: [11C]osimertinib
Description: Patients will receive 3 single IV microdose administrations of [11C]osimertinib and PET exams on: Day 1, Day 2 (or up to Day 8) and Day 29.Type: Drug[11C]osimertinib + oral osimertinib
Description: Measurement of the brain standard uptake value (SUV) seen on PET scan at baseline.
Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest Time: PET Scan on Day 1Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken at baseline.
Measure: Pharmacokinetics of [11C]osimertinib Time: Blood samples collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken at baseline.
Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC) Time: Measurement collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken at baseline.
Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax) Time: Blood samples collected on Day 1 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Measurement of the brain standard uptake value (SUV) seen on PET scan after a single dose of oral osimertinib.
Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest Time: PET Scan on Day 2Description: Measurement of the brain standard uptake value (SUV) seen on PET scan after at least 21days of continuous oral osimertinib dosing.
Measure: Brain Exposure to [11C]osimertinib in Tumour Region of Interest Time: PET Scan on Day 29Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Time: Blood samples collected on Day 292, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Pharmacokinetics of [11C]osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Time: Blood samples collected on Day 2 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax) Time: Blood samples collected on Day 2 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Pharmacokinetics of [11C]osimertinib radioactivity by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Radioactivity by Assessment of Time to Cmax (Tmax) Time: Blood samples collected on Day 29 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC) Time: Measurement collected on Day 2 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Measurement of the brain to plasma partition coefficient (concentration brain/plasma ratio) by assessment of area under the concentration-time curve, derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of [11C]osimertinib Brain to Plasma Ratio of Area Under the Concentration Curve (AUC) Time: Measurement collected on Day 29 at 2, 4, 6, 8, 10, 15, 20, 30, 40, 50, 60, 75, and 90 minutes post-[11C]osimertinib injection.Description: Pharmacokinetics of osimertinib and its metabolite by assessment of AUC metabolite to parent ratio, derived from the curves taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib and its Metabolite by Assessment of AUC Metabolite to Parent Ratio Time: Blood samples collected on Day 2 at pre-administration, 1, 2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib by Assessment of Maximum Plasma Concentration (Cmax) Time: Blood samples collected on Day 2 at pre-administration, 1, 2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of area under the concentration-time curve from time zero to the last measurable time point.
Measure: Pharmacokinetics of Osimertinib by Assessment of Area Under the Concentration-time Curve Time: Blood samples collected on Day 2 at pre-administration, 1, 2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib by Assessment of Time to Cmax (Tmax) Time: Blood samples collected on Day 2 at pre-administration, 1, 2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib and its metabolite by assessment of AUC metabolite to parent ratio, derived from the curves taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib and its Metabolite by Assessment of AUC Metabolite to Parent Ratio Time: Blood samples collected on Day 29 at pre-administration, 1,2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib by Assessment of Maximum Plasma Concentration (Cmax) Time: Blood samples collected on Day 29 at pre-administration, 1,2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of area under the concentration-time curve from time zero to the last measurable time point.
Measure: Pharmacokinetics of Osimertinib by Assessment of Area Under the Concentration-time Curve Time: Blood samples collected on Day 29 at pre-administration, 1,2,4 and 6 hours post dose.Description: Pharmacokinetics of osimertinib by assessment of time to Cmax (Tmax), derived from the curve taken during the treatment period.
Measure: Pharmacokinetics of Osimertinib by Assessment of Time to Cmax (Tmax) Time: Blood samples collected on Day 29 at pre-administration, 1,2,4 and 6 hours post dose.Description: Collection and assessment of adverse events graded using CTCAE (version 4.03).
Measure: Incidence of Treatment Emergent Adverse Events [Safety and Tolerability] with IV [11C]osimertinib administration Time: From study Day 1 and until 30 days after the study drug is discontinued.Description: Collection and assessment of adverse events using CTCAE (version 4.03)
Measure: Incidence of Treatment Emergent Adverse Events [Safety and Tolerability] with continuous oral osimertinib Time: From study Day 1 and until 30 days after the study drug is discontinued.Single Group Assignment
There are 3 SNPs
For TKI-naïve patients, confirmation of EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) as assessed by local and/or central laboratory via tissue/cytology is required. --- L858R ---
For TKI-naïve patients, confirmation of EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) as assessed by local and/or central laboratory via tissue/cytology is required. --- L858R --- --- L861Q ---
Patients must have documented radiological progression on the last treatment administered prior to enrolling in the study and should harbour the T790M EGFR resistance mutation - determined in tissue/cytology or in plasma. --- T790M ---